Harnessing the Power of INCAGN01949: Targeting Tumor-Specific Immunity and Regulatory T Cells in Cancer Therapy

OX40 is a T cell receptor that boosts signaling in CD4+ and CD8+ T cells during various stages of immune response. Preclinical studies in mice have demonstrated the effectiveness of anti-OX40 antibodies as a single treatment and in combination with other immunotherapy approaches, such as cancer vaccines. These antibodies are believed to work by activating OX40 in tumor-specific T cells to increase their sensitivity to tumor antigens and by engaging Fcγ receptors to selectively remove regulatory T cells within the tumor.

INCAGN01949 is a newly developed human IgG1 monoclonal antibody that targets OX40. It has been designed to enhance receptor signaling, leading to increased production of TNFα and IFNγ while reducing IL-10. This is achieved through the clustering of OX40 and activation of the NFκB pathway in T cells. INCAGN01949 also has the ability to engage activating Fcγ receptors on immune cells, which could selectively target regulatory T cells within tumors.

The properties of INCAGN01949 suggest its potential for clinical development, both as a standalone treatment and in combination with other immunotherapies. The study was presented at the 107th Annual Meeting of the American Association for Cancer Research and published in the Cancer Research journal.